The inhibition of histamine effects in the skin may be useful in predicting the clinical utility of newly introduced antihistamines in treating allergic disorders.
The effect of cetirizine on plasma membrane fluidity and
heterogeneity of human eosinophils, neutrophils, platelets and
lymphocytes was investigated using a fluorescence technique.
Membrane fluidity and heterogeneity were studied by measuring the
steady-state fluorescence anisotropy and fluorescence decay of 1-(4-
trimethylammonium-phenyl)-6-phenyl-1, 3, 5-hexatriene (TMA-DPH)
incorporated in the membrane. The results demonstrate that
cetirizine (1 μg/ml) induced a significant increase in the
Hpid order in the exterior part of the membrane and a decrease in
membrane heterogeneity in eosinophils, neutrophils and platelets.
Moreover, cetirizine blocked the PAF induced changes in membrane
fluidity in these cells. Cetirizine did not influence significantly
the plasma membrane of lymphocytes. These data may partially explain
the effect ofcetirizine on inflammatory cell activities.
1 We investigated the effect of 2 weeks therapy with oral cetirizine (10 mg twice daily) on methacholine bronchial reactivity in 14 asthmatics. All had bronchial hyperreactivity to methacholine on entry to the study, with a geometric mean cumulative PC20 of 0.83 mg ml-' (range 0.1-3.61 mg ml-') and eight were atopic on skin prick testing. 2 The study was placebo-controlled and in randomised order, with a minimum 1 month washout period between cetirizine and placebo study periods. Four methacholine challenges were performed in all, at the beginning and at the end of each study period. 3 No significant change in methacholine reactivity was found following 2 weeks therapy with cetirizine. The repeatability coefficient for the PC20 methacholine over 2 weeks was found to be 2.90 doubling dilutions for the placebo period and 1.73 doubling dilutions for the cetirizine period. The study had a 80% power at the 5% significance level (twotailed) to detect a 1.16-doubling concentration change in methacholine reactivity. 4 We conclude that 2 weeks therapy with cetirizine has no significant effect on nonspecific bronchial hyperreactivity.
The effects of oral administration of the antihistamine cetirizine on the weal and flare caused by intradermal injection of platelet activating factor (PAF-acether), kallikrein, histamine and the patient's own serum were investigated in 10 patients with chronic urticaria. Cetirizine markedly reduced the weal and flare induced by all these agents as measured 12 min after the injections. The delayed reactions observed after injection of PAF, kallikrein and serum were also inhibited by cetirizine at 6 hours. In addition, reactions which were present 20 h after injection of the agent before administration of cetirizine were found to be inhibited at the same point in time after cetirizine treatment. These effects might explain the good inhibitory clinical effect of cetirizine on the patients' urticaria. No side-effects were noted during the treatment.
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